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#437395 Microsoft Had a Crazy Idea to Put ...

A little over two years ago, a shipping container-sized cylinder bearing Microsoft’s name and logo was lowered onto the ocean floor off the northern coast of Scotland. Inside were 864 servers, and their submersion was part of the second phase of the software giant’s Project Natick. Launched in 2015, the project’s purpose is to determine the feasibility of underwater data centers powered by offshore renewable energy.

A couple months ago, the deep-sea servers were brought back up to the surface so engineers could inspect them and evaluate how they’d performed while under water.

But wait—why were they there in the first place?

As bizarre as it seems to sink hundreds of servers into the ocean, there are actually several very good reasons to do so. According to the UN, about 40 percent of the world’s population lives within 60 miles of an ocean. As internet connectivity expands to cover most of the globe in the next few years, millions more people will come online, and a lot more servers will be needed to manage the increased demand and data they’ll generate.

In densely-populated cities real estate is expensive and can be hard to find. But know where there’s lots of cheap, empty space? At the bottom of the ocean. This locale also carries the added benefit of being really cold (depending where we’re talking, that is; if you’re looking off the coast of, say, Mumbai or Abu Dhabi, the waters are warmer).

Servers generate a lot of heat, and datacenters use most of their electricity for cooling. Keeping not just the temperature but also the humidity level constant is important for optimal functioning of the servers; neither of these vary much 100 feet under water.

Finally, installing data centers on the ocean floor is, surprisingly, much faster than building them on land. Microsoft claims its server-holding cylinders will take less than 90 days to go from factory ship to operation, as compared to the average two years it takes to get a terrestrial data center up and running.

Microsoft’s Special Projects team operated the underwater data center for two years, and it took a full day to dredge it up and bring it to the surface. One of the first things researchers did was to insert test tubes into the container to take samples of the air inside; they’ll use it to try to determine how gases released from the equipment may have impacted the servers’ operating environment.

The container was filled with dry nitrogen upon deployment, which seems to have made for a much better environment than the oxygen that land-bound servers are normally surrounded by; the failure rate of the servers in the water was just one-eighth that of Microsoft’s typical rate for its servers on land. The team thinks the nitrogen atmosphere was helpful because it’s less corrosive than oxygen. The fact that no humans entered the container for the entirety of its operations helped, too (no moving around of components or having to turn on lights or adjust the temperature).

Ben Cutler, a project manager in Microsoft’s Special Projects research group who leads Project Natick, believes the results of this phase of the project are sufficient to show that underwater data centers are worth pursuing. “We are now at the point of trying to harness what we have done as opposed to feeling the need to go and prove out some more,” he said.

Cutler envisions putting underwater datacenters near offshore wind farms to power them sustainably. The data centers of the future will require less human involvement, instead being managed and run primarily by technologies like robotics and AI. In this kind of “lights-out” datacenter, the servers would be swapped out about once every five years, with any that fail before then being taken offline.

The final step in this phase of Project Natick is to recycle all the components used for the underwater data center, including the steel pressure vessel, heat exchangers, and the servers themselves—and restoring the sea bed where the cylinder rested back to its original condition.

If Cutler’s optimism is a portent of things to come, it may not be long before the ocean floor is dotted with sustainable datacenters to feed our ever-increasing reliance on our phones and the internet.

Image Credit: Microsoft Continue reading

Posted in Human Robots

#437373 Microsoft’s New Deepfake Detector Puts ...

The upcoming US presidential election seems set to be something of a mess—to put it lightly. Covid-19 will likely deter millions from voting in person, and mail-in voting isn’t shaping up to be much more promising. This all comes at a time when political tensions are running higher than they have in decades, issues that shouldn’t be political (like mask-wearing) have become highly politicized, and Americans are dramatically divided along party lines.

So the last thing we need right now is yet another wrench in the spokes of democracy, in the form of disinformation; we all saw how that played out in 2016, and it wasn’t pretty. For the record, disinformation purposely misleads people, while misinformation is simply inaccurate, but without malicious intent. While there’s not a ton tech can do to make people feel safe at crowded polling stations or up the Postal Service’s budget, tech can help with disinformation, and Microsoft is trying to do so.

On Tuesday the company released two new tools designed to combat disinformation, described in a blog post by VP of Customer Security and Trust Tom Burt and Chief Scientific Officer Eric Horvitz.

The first is Microsoft Video Authenticator, which is made to detect deepfakes. In case you’re not familiar with this wicked byproduct of AI progress, “deepfakes” refers to audio or visual files made using artificial intelligence that can manipulate peoples’ voices or likenesses to make it look like they said things they didn’t. Editing a video to string together words and form a sentence someone didn’t say doesn’t count as a deepfake; though there’s manipulation involved, you don’t need a neural network and you’re not generating any original content or footage.

The Authenticator analyzes videos or images and tells users the percentage chance that they’ve been artificially manipulated. For videos, the tool can even analyze individual frames in real time.

Deepfake videos are made by feeding hundreds of hours of video of someone into a neural network, “teaching” the network the minutiae of the person’s voice, pronunciation, mannerisms, gestures, etc. It’s like when you do an imitation of your annoying coworker from accounting, complete with mimicking the way he makes every sentence sound like a question and his eyes widen when he talks about complex spreadsheets. You’ve spent hours—no, months—in his presence and have his personality quirks down pat. An AI algorithm that produces deepfakes needs to learn those same quirks, and more, about whoever the creator’s target is.

Given enough real information and examples, the algorithm can then generate its own fake footage, with deepfake creators using computer graphics and manually tweaking the output to make it as realistic as possible.

The scariest part? To make a deepfake, you don’t need a fancy computer or even a ton of knowledge about software. There are open-source programs people can access for free online, and as far as finding video footage of famous people—well, we’ve got YouTube to thank for how easy that is.

Microsoft’s Video Authenticator can detect the blending boundary of a deepfake and subtle fading or greyscale elements that the human eye may not be able to see.

In the blog post, Burt and Horvitz point out that as time goes by, deepfakes are only going to get better and become harder to detect; after all, they’re generated by neural networks that are continuously learning from and improving themselves.

Microsoft’s counter-tactic is to come in from the opposite angle, that is, being able to confirm beyond doubt that a video, image, or piece of news is real (I mean, can McDonald’s fries cure baldness? Did a seal slap a kayaker in the face with an octopus? Never has it been so imperative that the world know the truth).

A tool built into Microsoft Azure, the company’s cloud computing service, lets content producers add digital hashes and certificates to their content, and a reader (which can be used as a browser extension) checks the certificates and matches the hashes to indicate the content is authentic.

Finally, Microsoft also launched an interactive “Spot the Deepfake” quiz it developed in collaboration with the University of Washington’s Center for an Informed Public, deepfake detection company Sensity, and USA Today. The quiz is intended to help people “learn about synthetic media, develop critical media literacy skills, and gain awareness of the impact of synthetic media on democracy.”

The impact Microsoft’s new tools will have remains to be seen—but hey, we’re glad they’re trying. And they’re not alone; Facebook, Twitter, and YouTube have all taken steps to ban and remove deepfakes from their sites. The AI Foundation’s Reality Defender uses synthetic media detection algorithms to identify fake content. There’s even a coalition of big tech companies teaming up to try to fight election interference.

One thing is for sure: between a global pandemic, widespread protests and riots, mass unemployment, a hobbled economy, and the disinformation that’s remained rife through it all, we’re going to need all the help we can get to make it through not just the election, but the rest of the conga-line-of-catastrophes year that is 2020.

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Posted in Human Robots

#437303 The Deck Is Not Rigged: Poker and the ...

Tuomas Sandholm, a computer scientist at Carnegie Mellon University, is not a poker player—or much of a poker fan, in fact—but he is fascinated by the game for much the same reason as the great game theorist John von Neumann before him. Von Neumann, who died in 1957, viewed poker as the perfect model for human decision making, for finding the balance between skill and chance that accompanies our every choice. He saw poker as the ultimate strategic challenge, combining as it does not just the mathematical elements of a game like chess but the uniquely human, psychological angles that are more difficult to model precisely—a view shared years later by Sandholm in his research with artificial intelligence.

“Poker is the main benchmark and challenge program for games of imperfect information,” Sandholm told me on a warm spring afternoon in 2018, when we met in his offices in Pittsburgh. The game, it turns out, has become the gold standard for developing artificial intelligence.

Tall and thin, with wire-frame glasses and neat brow hair framing a friendly face, Sandholm is behind the creation of three computer programs designed to test their mettle against human poker players: Claudico, Libratus, and most recently, Pluribus. (When we met, Libratus was still a toddler and Pluribus didn’t yet exist.) The goal isn’t to solve poker, as such, but to create algorithms whose decision making prowess in poker’s world of imperfect information and stochastic situations—situations that are randomly determined and unable to be predicted—can then be applied to other stochastic realms, like the military, business, government, cybersecurity, even health care.

While the first program, Claudico, was summarily beaten by human poker players—“one broke-ass robot,” an observer called it—Libratus has triumphed in a series of one-on-one, or heads-up, matches against some of the best online players in the United States.

Libratus relies on three main modules. The first involves a basic blueprint strategy for the whole game, allowing it to reach a much faster equilibrium than its predecessor. It includes an algorithm called the Monte Carlo Counterfactual Regret Minimization, which evaluates all future actions to figure out which one would cause the least amount of regret. Regret, of course, is a human emotion. Regret for a computer simply means realizing that an action that wasn’t chosen would have yielded a better outcome than one that was. “Intuitively, regret represents how much the AI regrets having not chosen that action in the past,” says Sandholm. The higher the regret, the higher the chance of choosing that action next time.

It’s a useful way of thinking—but one that is incredibly difficult for the human mind to implement. We are notoriously bad at anticipating our future emotions. How much will we regret doing something? How much will we regret not doing something else? For us, it’s an emotionally laden calculus, and we typically fail to apply it in quite the right way. For a computer, it’s all about the computation of values. What does it regret not doing the most, the thing that would have yielded the highest possible expected value?

The second module is a sub-game solver that takes into account the mistakes the opponent has made so far and accounts for every hand she could possibly have. And finally, there is a self-improver. This is the area where data and machine learning come into play. It’s dangerous to try to exploit your opponent—it opens you up to the risk that you’ll get exploited right back, especially if you’re a computer program and your opponent is human. So instead of attempting to do that, the self-improver lets the opponent’s actions inform the areas where the program should focus. “That lets the opponent’s actions tell us where [they] think they’ve found holes in our strategy,” Sandholm explained. This allows the algorithm to develop a blueprint strategy to patch those holes.

It’s a very human-like adaptation, if you think about it. I’m not going to try to outmaneuver you head on. Instead, I’m going to see how you’re trying to outmaneuver me and respond accordingly. Sun-Tzu would surely approve. Watch how you’re perceived, not how you perceive yourself—because in the end, you’re playing against those who are doing the perceiving, and their opinion, right or not, is the only one that matters when you craft your strategy. Overnight, the algorithm patches up its overall approach according to the resulting analysis.

There’s one final thing Libratus is able to do: play in situations with unknown probabilities. There’s a concept in game theory known as the trembling hand: There are branches of the game tree that, under an optimal strategy, one should theoretically never get to; but with some probability, your all-too-human opponent’s hand trembles, they take a wrong action, and you’re suddenly in a totally unmapped part of the game. Before, that would spell disaster for the computer: An unmapped part of the tree means the program no longer knows how to respond. Now, there’s a contingency plan.

Of course, no algorithm is perfect. When Libratus is playing poker, it’s essentially working in a zero-sum environment. It wins, the opponent loses. The opponent wins, it loses. But while some real-life interactions really are zero-sum—cyber warfare comes to mind—many others are not nearly as straightforward: My win does not necessarily mean your loss. The pie is not fixed, and our interactions may be more positive-sum than not.

What’s more, real-life applications have to contend with something that a poker algorithm does not: the weights that are assigned to different elements of a decision. In poker, this is a simple value-maximizing process. But what is value in the human realm? Sandholm had to contend with this before, when he helped craft the world’s first kidney exchange. Do you want to be more efficient, giving the maximum number of kidneys as quickly as possible—or more fair, which may come at a cost to efficiency? Do you want as many lives as possible saved—or do some take priority at the cost of reaching more? Is there a preference for the length of the wait until a transplant? Do kids get preference? And on and on. It’s essential, Sandholm says, to separate means and the ends. To figure out the ends, a human has to decide what the goal is.

“The world will ultimately become a lot safer with the help of algorithms like Libratus,” Sandholm told me. I wasn’t sure what he meant. The last thing that most people would do is call poker, with its competition, its winners and losers, its quest to gain the maximum edge over your opponent, a haven of safety.

“Logic is good, and the AI is much better at strategic reasoning than humans can ever be,” he explained. “It’s taking out irrationality, emotionality. And it’s fairer. If you have an AI on your side, it can lift non-experts to the level of experts. Naïve negotiators will suddenly have a better weapon. We can start to close off the digital divide.”

It was an optimistic note to end on—a zero-sum, competitive game yielding a more ultimately fair and rational world.

I wanted to learn more, to see if it was really possible that mathematics and algorithms could ultimately be the future of more human, more psychological interactions. And so, later that day, I accompanied Nick Nystrom, the chief scientist of the Pittsburgh Supercomputing Center—the place that runs all of Sandholm’s poker-AI programs—to the actual processing center that make undertakings like Libratus possible.

A half-hour drive found us in a parking lot by a large glass building. I’d expected something more futuristic, not the same square, corporate glass squares I’ve seen countless times before. The inside, however, was more promising. First the security checkpoint. Then the ride in the elevator — down, not up, to roughly three stories below ground, where we found ourselves in a maze of corridors with card readers at every juncture to make sure you don’t slip through undetected. A red-lit panel formed the final barrier, leading to a small sliver of space between two sets of doors. I could hear a loud hum coming from the far side.

“Let me tell you what you’re going to see before we walk in,” Nystrom told me. “Once we get inside, it will be too loud to hear.”

I was about to witness the heart of the supercomputing center: 27 large containers, in neat rows, each housing multiple processors with speeds and abilities too great for my mind to wrap around. Inside, the temperature is by turns arctic and tropic, so-called “cold” rows alternating with “hot”—fans operate around the clock to cool the processors as they churn through millions of giga, mega, tera, peta and other ever-increasing scales of data bytes. In the cool rows, robotic-looking lights blink green and blue in orderly progression. In the hot rows, a jumble of multicolored wires crisscrosses in tangled skeins.

In the corners stood machines that had outlived their heyday. There was Sherlock, an old Cray model, that warmed my heart. There was a sad nameless computer, whose anonymity was partially compensated for by the Warhol soup cans adorning its cage (an homage to Warhol’s Pittsburghian origins).

And where does Libratus live, I asked? Which of these computers is Bridges, the computer that runs the AI Sandholm and I had been discussing?

Bridges, it turned out, isn’t a single computer. It’s a system with processing power beyond comprehension. It takes over two and a half petabytes to run Libratus. A single petabyte is a million gigabytes: You could watch over 13 years of HD video, store 10 billion photos, catalog the contents of the entire Library of Congress word for word. That’s a whole lot of computing power. And that’s only to succeed at heads-up poker, in limited circumstances.

Yet despite the breathtaking computing power at its disposal, Libratus is still severely limited. Yes, it beat its opponents where Claudico failed. But the poker professionals weren’t allowed to use many of the tools of their trade, including the opponent analysis software that they depend on in actual online games. And humans tire. Libratus can churn for a two-week marathon, where the human mind falters.

But there’s still much it can’t do: play more opponents, play live, or win every time. There’s more humanity in poker than Libratus has yet conquered. “There’s this belief that it’s all about statistics and correlations. And we actually don’t believe that,” Nystrom explained as we left Bridges behind. “Once in a while correlations are good, but in general, they can also be really misleading.”

Two years later, the Sandholm lab will produce Pluribus. Pluribus will be able to play against five players—and will run on a single computer. Much of the human edge will have evaporated in a short, very short time. The algorithms have improved, as have the computers. AI, it seems, has gained by leaps and bounds.

So does that mean that, ultimately, the algorithmic can indeed beat out the human, that computation can untangle the web of human interaction by discerning “the little tactics of deception, of asking yourself what is the other man going to think I mean to do,” as von Neumann put it?

Long before I’d spoken to Sandholm, I’d met Kevin Slavin, a polymath of sorts whose past careers have including founding a game design company and an interactive art space and launching the Playful Systems group at MIT’s Media Lab. Slavin has a decidedly different view from the creators of Pluribus. “On the one hand, [von Neumann] was a genius,” Kevin Slavin reflects. “But the presumptuousness of it.”

Slavin is firmly on the side of the gambler, who recognizes uncertainty for what it is and thus is able to take calculated risks when necessary, all the while tampering confidence at the outcome. The most you can do is put yourself in the path of luck—but to think you can guess with certainty the actual outcome is a presumptuousness the true poker player foregoes. For Slavin, the wonder of computers is “That they can generate this fabulous, complex randomness.” His opinion of the algorithmic assaults on chance? “This is their moment,” he said. “But it’s the exact opposite of what’s really beautiful about a computer, which is that it can do something that’s actually unpredictable. That, to me, is the magic.”

Will they actually succeed in making the unpredictable predictable, though? That’s what I want to know. Because everything I’ve seen tells me that absolute success is impossible. The deck is not rigged.

“It’s an unbelievable amount of work to get there. What do you get at the end? Let’s say they’re successful. Then we live in a world where there’s no God, agency, or luck,” Slavin responded.

“I don’t want to live there,’’ he added “I just don’t want to live there.”

Luckily, it seems that for now, he won’t have to. There are more things in life than are yet written in the algorithms. We have no reliable lie detection software—whether in the face, the skin, or the brain. In a recent test of bluffing in poker, computer face recognition failed miserably. We can get at discomfort, but we can’t get at the reasons for that discomfort: lying, fatigue, stress—they all look much the same. And humans, of course, can also mimic stress where none exists, complicating the picture even further.

Pluribus may turn out to be powerful, but von Neumann’s challenge still stands: The true nature of games, the most human of the human, remains to be conquered.

This article was originally published on Undark. Read the original article.

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#437258 This Startup Is 3D Printing Custom ...

Around 1.9 million people in the US are currently living with limb loss. The trauma of losing a limb is just the beginning of what amputees have to face, with the sky-high cost of prosthetics making their circumstance that much more challenging.

Prosthetics can run over $50,000 for a complex limb (like an arm or a leg) and aren’t always covered by insurance. As if shelling out that sum one time wasn’t costly enough, kids’ prosthetics need to be replaced as they outgrow them, meaning the total expense can reach hundreds of thousands of dollars.

A startup called Unlimited Tomorrow is trying to change this, and using cutting-edge technology to do so. Based in Rhinebeck, New York, a town about two hours north of New York City, the company was founded by 23-year-old Easton LaChappelle. He’d been teaching himself the basics of robotics and building prosthetics since grade school (his 8th grade science fair project was a robotic arm) and launched his company in 2014.

After six years of research and development, the company launched its TrueLimb product last month, describing it as an affordable, next-generation prosthetic arm using a custom remote-fitting process where the user never has to leave home.

The technologies used for TrueLimb’s customization and manufacturing are pretty impressive, in that they both cut costs and make the user’s experience a lot less stressful.

For starters, the entire purchase, sizing, and customization process for the prosthetic can be done remotely. Here’s how it works. First, prospective users fill out an eligibility form and give information about their residual limb. If they’re a qualified candidate for a prosthetic, Unlimited Tomorrow sends them a 3D scanner, which they use to scan their residual limb.

The company uses the scans to design a set of test sockets (the component that connects the residual limb to the prosthetic), which are mailed to the user. The company schedules a video meeting with the user for them to try on and discuss the different sockets, with the goal of finding the one that’s most comfortable; new sockets can be made based on the information collected during the video consultation. The user selects their skin tone from a swatch with 450 options, then Unlimited Tomorrow 3D prints and assembles the custom prosthetic and tests it before shipping it out.

“We print the socket, forearm, palm, and all the fingers out of durable nylon material in full color,” LaChappelle told Singularity Hub in an email. “The only components that aren’t 3D printed are the actuators, tendons, electronics, batteries, sensors, and the nuts and bolts. We are an extreme example of final use 3D printing.”

Unlimited Tomorrow’s website lists TrueLimb’s cost as “as low as $7,995.” When you consider the customization and capabilities of the prosthetic, this is incredibly low. According to LaChappelle, the company created a muscle sensor that picks up muscle movement at a higher resolution than the industry standard electromyography sensors. The sensors read signals from nerves in the residual limb used to control motions like fingers bending. This means that when a user thinks about bending a finger, the nerve fires and the prosthetic’s sensors can detect the signal and translate it into the action.

“Working with children using our device, I’ve witnessed a physical moment where the brain “clicks” and starts moving the hand rather than focusing on moving the muscles,” LaChappelle said.

The cost savings come both from the direct-to-consumer model and the fact that Unlimited Tomorrow doesn’t use any outside suppliers. “We create every piece of our product,” LaChappelle said. “We don’t rely on another prosthetic manufacturer to make expensive sensors or electronics. By going direct to consumer, we cut out all the middlemen that usually drive costs up.” Similar devices on the market can cost up to $100,000.

Unlimited Tomorrow is primarily focused on making prosthetics for kids; when they outgrow their first TrueLimb, they send it back, where the company upcycles the expensive quality components and integrates them into a new customized device.

Unlimited Tomorrow isn’t the first to use 3D printing for prosthetics. Florida-based Limbitless Solutions does so too, and industry experts believe the technology is the future of artificial limbs.

“I am constantly blown away by this tech,” LaChappelle said. “We look at technology as the means to augment the human body and empower people.”

Image Credit: Unlimited Tomorrow Continue reading

Posted in Human Robots

#437171 Scientists Tap the World’s Most ...

In The Hitchhiker’s Guide to the Galaxy by Douglas Adams, the haughty supercomputer Deep Thought is asked whether it can find the answer to the ultimate question concerning life, the universe, and everything. It replies that, yes, it can do it, but it’s tricky and it’ll have to think about it. When asked how long it will take it replies, “Seven-and-a-half million years. I told you I’d have to think about it.”

Real-life supercomputers are being asked somewhat less expansive questions but tricky ones nonetheless: how to tackle the Covid-19 pandemic. They’re being used in many facets of responding to the disease, including to predict the spread of the virus, to optimize contact tracing, to allocate resources and provide decisions for physicians, to design vaccines and rapid testing tools, and to understand sneezes. And the answers are needed in a rather shorter time frame than Deep Thought was proposing.

The largest number of Covid-19 supercomputing projects involves designing drugs. It’s likely to take several effective drugs to treat the disease. Supercomputers allow researchers to take a rational approach and aim to selectively muzzle proteins that SARS-CoV-2, the virus that causes Covid-19, needs for its life cycle.

The viral genome encodes proteins needed by the virus to infect humans and to replicate. Among these are the infamous spike protein that sniffs out and penetrates its human cellular target, but there are also enzymes and molecular machines that the virus forces its human subjects to produce for it. Finding drugs that can bind to these proteins and stop them from working is a logical way to go.

The Summit supercomputer at Oak Ridge National Laboratory has a peak performance of 200,000 trillion calculations per second—equivalent to about a million laptops. Image credit: Oak Ridge National Laboratory, U.S. Dept. of Energy, CC BY

I am a molecular biophysicist. My lab, at the Center for Molecular Biophysics at the University of Tennessee and Oak Ridge National Laboratory, uses a supercomputer to discover drugs. We build three-dimensional virtual models of biological molecules like the proteins used by cells and viruses, and simulate how various chemical compounds interact with those proteins. We test thousands of compounds to find the ones that “dock” with a target protein. Those compounds that fit, lock-and-key style, with the protein are potential therapies.

The top-ranked candidates are then tested experimentally to see if they indeed do bind to their targets and, in the case of Covid-19, stop the virus from infecting human cells. The compounds are first tested in cells, then animals, and finally humans. Computational drug discovery with high-performance computing has been important in finding antiviral drugs in the past, such as the anti-HIV drugs that revolutionized AIDS treatment in the 1990s.

World’s Most Powerful Computer
Since the 1990s the power of supercomputers has increased by a factor of a million or so. Summit at Oak Ridge National Laboratory is presently the world’s most powerful supercomputer, and has the combined power of roughly a million laptops. A laptop today has roughly the same power as a supercomputer had 20-30 years ago.

However, in order to gin up speed, supercomputer architectures have become more complicated. They used to consist of single, very powerful chips on which programs would simply run faster. Now they consist of thousands of processors performing massively parallel processing in which many calculations, such as testing the potential of drugs to dock with a pathogen or cell’s proteins, are performed at the same time. Persuading those processors to work together harmoniously is a pain in the neck but means we can quickly try out a lot of chemicals virtually.

Further, researchers use supercomputers to figure out by simulation the different shapes formed by the target binding sites and then virtually dock compounds to each shape. In my lab, that procedure has produced experimentally validated hits—chemicals that work—for each of 16 protein targets that physician-scientists and biochemists have discovered over the past few years. These targets were selected because finding compounds that dock with them could result in drugs for treating different diseases, including chronic kidney disease, prostate cancer, osteoporosis, diabetes, thrombosis and bacterial infections.

Scientists are using supercomputers to find ways to disable the various proteins—including the infamous spike protein (green protrusions)—produced by SARS-CoV-2, the virus responsible for Covid-19. Image credit: Thomas Splettstoesser scistyle.com, CC BY-ND

Billions of Possibilities
So which chemicals are being tested for Covid-19? A first approach is trying out drugs that already exist for other indications and that we have a pretty good idea are reasonably safe. That’s called “repurposing,” and if it works, regulatory approval will be quick.

But repurposing isn’t necessarily being done in the most rational way. One idea researchers are considering is that drugs that work against protein targets of some other virus, such as the flu, hepatitis or Ebola, will automatically work against Covid-19, even when the SARS-CoV-2 protein targets don’t have the same shape.

Our own work has now expanded to about 10 targets on SARS-CoV-2, and we’re also looking at human protein targets for disrupting the virus’s attack on human cells. Top-ranked compounds from our calculations are being tested experimentally for activity against the live virus. Several of these have already been found to be active.The best approach is to check if repurposed compounds will actually bind to their intended target. To that end, my lab published a preliminary report of a supercomputer-driven docking study of a repurposing compound database in mid-February. The study ranked 8,000 compounds in order of how well they bind to the viral spike protein. This paper triggered the establishment of a high-performance computing consortium against our viral enemy, announced by President Trump in March. Several of our top-ranked compounds are now in clinical trials.

Also, we and others are venturing out into the wild world of new drug discovery for Covid-19—looking for compounds that have never been tried as drugs before. Databases of billions of these compounds exist, all of which could probably be synthesized in principle but most of which have never been made. Billion-compound docking is a tailor-made task for massively parallel supercomputing.

Dawn of the Exascale Era
Work will be helped by the arrival of the next big machine at Oak Ridge, called Frontier, planned for next year. Frontier should be about 10 times more powerful than Summit. Frontier will herald the “exascale” supercomputing era, meaning machines capable of 1,000,000,000,000,000,000 calculations per second.

Although some fear supercomputers will take over the world, for the time being, at least, they are humanity’s servants, which means that they do what we tell them to. Different scientists have different ideas about how to calculate which drugs work best—some prefer artificial intelligence, for example—so there’s quite a lot of arguing going on.

Hopefully, scientists armed with the most powerful computers in the world will, sooner rather than later, find the drugs needed to tackle Covid-19. If they do, then their answers will be of more immediate benefit, if less philosophically tantalizing, than the answer to the ultimate question provided by Deep Thought, which was, maddeningly, simply 42.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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